This project contains studies aimed at elucidating genetically controlled host defense mechanisms involved in spontaneous recovery and protective immunity against Friend murine retrovirus-induced leukemia. MHC genes play an important role both in spontaneous recovery and in protective immunity induced by vaccination. Our recent results show that point mutations in either the I-Ab gene or the Db gene are sufficient to inhibit spontaneous recovery. The I-Ab gene acts as a typical immune response gene facilitating the T helper cell response to Friend virus envelope protein. The Db gene appears to influence development of virus-specific cytotoxic T lymphocytes. These cells are strongly associated with the actual recovery process in vivo, and our current data indicates that they are specific for the viral envelope protein. The Db haplotype may operate to facilitate recovery by selecting certain viral envelope peptides as targets for immune lysis. Protective immunity can be induced in this system by inoculation with killed whole virus or purified viral envelope protein in adjuvant or recombinant vaccinia virus expressing the viral envelope protein. The I-Ab gene is important in mediating a successful response to immunization, but animals lacking this gene can be protected if immunization is done using a powerful adjuvant. Recent data indicates that some synthetic vaccines feasible for use in humans also work to potentiate successful immune protection in this model.